tbuckley/cabot-search huggingface dataset:
Health-related quality of life among patients with multiple myeloma treated with CAR-T therapy.
Authors: Samantha Jane Gagnon, Ajay K. Nooka
Journal: Journal of Clinical Oncology (2023)

e20040 Background: The regulatory approvals in myeloma were predominantly based on the safety and efficacy of the antimyeloma therapies. Health-related quality of life (HRQOL) metrics have not routinely been incorporated into these studies, nor were they a requirement for approval, which explains the dearth of HRQOL studies in myeloma. Recent approvals of chimeric antigen receptor T-cell (CAR-T) therapy targeting the B-cell maturation antigen were no different. While improved clinical outcomes in myeloma led to the FDA and EMA approvals, the CAR-T effects on HRQOL are not well described. Methods: We conducted a cross-sectional observational pilot study to evaluate HRQOL among patients that received CAR-T. Inclusion criteria were age &gt;/= 18 years with a diagnosis of myeloma, had been treated with an autologous CAR-T a minimum of 56 days prior to survey date and had not yet experienced progression as defined by the IMWG criteria. HRQOL measurements were obtained using validated tool, self-administered FACT-MM questionnaire post-CAR-T infusion. The primary endpoint measurement was the FACT-MM composite score. Associations between FACT-MM scores and predictors were analyzed using nonparametric tests. FACT-MM and subscores were analyzed as continuous and dichotomous outcomes. Results: Between December 2021 and July 2022, 22 patients were enrolled (male: 54.55%, white: 54.55%). The median age of patients was 64 (range, 43-86) and the median time to enroll on the study from diagnosis is 6.5 years (3.5-17). Median FACT-MM score was 137.5 (IQR: 18.5) out of a maximum possible score of 164. The median trial outcome index (TOI) which is the sum of the physical and functional well-being (PWB and FWB), a predictor for physical and functional outcomes from treatment (FACIT) was 95 (IQR: 17) out of maximum possible 112. Other descriptive variables of interest were shown in the table. Differences in TOI were found between races (White, African American (AA), &amp; Asian p = 0.04). In our sample, AA and Asian subjects had higher median TOI, therefore race should not be considered to have a negative impact on clinical trial success. Subjects with a history of Gilbert’s syndrome (2 vs 20), reported higher overall FACT-MM scores (p = p=0.04), PWB (p=0.03) and pain-related HRQOL (p = 0.04). Interestingly, we did not find that HRQOL differed by patients that had evidence of CRS or ICANS during CAR-T therapy, or by age, R-ISS, CCI, presence of EMD or prior lines of therapy (LOT). Conclusions: Patients treated with CAR-T have reported high HRQOL metrics at least 2 months out from infusion. Age, RISS, CCI, prior LOT did not impact the HRQOL and may not be the sole criteria used for decision making whether or not to offer CAR-T. [Table: see text]
OMNIA-2: Phase I/II study of ANV419, an IL-2R-βγ targeted antibody-IL-2 fusion protein, in patients with relapsed or refractory multiple myeloma.
Authors: Dagmar Hess, Katrine Fladeland Iversen, Maria-Victoria Mateos, Thomas Pabst, Laura Rosiñol, Jana Kovacikova, Sangeeta Jethwa Schnetzler
Journal: Journal of Clinical Oncology (2023)

TPS8068 Background: ANV419 is a potent, selective IL-2Rβγ targeted antibody IL-2 fusion protein, designed to enable the delivery of high dose interleukin-2 (IL-2) to patients, in order to stimulate anti-tumour response and minimise toxicities. The ANV419-001 first-in-human study (NCT 04855929) demonstrated that ANV419 preferentially stimulates cytotoxic CD8+ T and natural killer (NK) cells over immunosuppressive regulatory T cells, with a significantly longer half-life than that of conventional IL-2. The safety and tolerability data from this study confirmed that ANV419 delivers high molar equivalents of IL-2 in a tolerable and convenient way. In patients with multiple myeloma, the critical role of NK cells has been well described. ANV419 is expected to promote antitumor response via the preferential stimulation of cytotoxic CD8+ T and NK cells. Methods: The OMNIA-2 study (ANV419-102; NCT 05641324) will evaluate safety and preliminary efficacy of ANV419 as monotherapy and in combination with daratumumab (dara), or lenalidomide with low dose dexamethasone (lena/dex), in patients with relapsed or refractory multiple myeloma. OMNIA-2 is a Phase I open-label, multi-center study in adult patients (n = 52) with symptomatic multiple myeloma who responded to previous treatment and received autologous stem cell transplant, or at least 2 lines of therapy including an immunomodulator, proteasome inhibitor, and/or dara. The study is conducted in 2 stages using a Bayesian Optimal Phase 2 approach. Stage 1 consists of a run-in phase with subsequent randomization to ANV419 243mcg/kg or ANV419 108mcg/kg for 8 weeks, followed by a second randomisation to ANV419 108mcg/kg in combination with lena/dex or dara for a further 8 weeks. Stage 2 follows a similar design as stage 1 and consists of a monotherapy run-in phase with either high or low dose ANV419, with a second randomisation to ANV419 108mcg/kg in combination with either lena/dex or dara, according to the safety and efficacy observed in Stage 1. ANV419 is administered intravenously over 15 to 20 minutes every two weeks. Lena, dex and dara are administered at their respective approved dosing regimens. Tumour response is determined using IMWG (2016) response criteria. AEs are assessed according to CTCAE V5.0. OMNIA-2 is being conducted in Denmark, France, Germany, Spain, Switzerland, UK and enrolment began in January 2023 and preliminary data are expected in Q1 2024. Clinical trial information: NCT05641324 .
Effect of dual properties of regorafenib in osteosarcoma on tumor progression and bone parameters in mouse preclinical models.
Authors: Javier Munoz Garcia, Jorge William Vargas-Franco, Emmanuelle Bompas, Denis Cochonneau, Emilie Ollivier, Jerome Kerzerho, Mehdi Brahmi, Jean-Yves Blay, Maire-Francoise Heymann, Frederic Lezot, Dominique Heymann
Journal: Journal of Clinical Oncology (2023)

e23501 Background: Osteosarcoma (OS) constitutes the most frequent malignant primary bone tumor in children and young adults. Actual treatments in OS are based in a multimodal therapy that combines pre- and post-surgery polychemotherapies including cisplatin, doxorubicin, ifosfamide and/or methotrexate. Regardless the use of this polychemotherapeutic approach, the five years overall survival for patients has not improved during the last four decades and there is a clinical need to identify new active drugs in OS. An interesting strategy implies the use of compounds that showed therapeutic benefits in other solid tumors. Regorafenib, a small molecule with multi-target tyrosine kinase inhibitory activity against FGFR-1 and -2, KIT, PDGFR, RAF, RET, TIE2 and VEGFR-1, -2 and -3, showed an anti-angiogenic/oncogenic properties in various solid tumors that includes metastatic colorectal cancer, hepatocarcinoma and breast cancer. In addition, regorafenib also inhibits in vitro the proliferation of several pediatric solid tumor cell lines such as rhabdomyosarcoma, Ewing sarcoma and OS. Methods: The present work aims to decipher the in vitro and in vivo effects of regorafenib in OS preclinical models. Results: The treatment of MNNG-HOS, KHOS and 143B osteosarcoma cell lines with Regorafenib resulted in the inhibition of cell proliferation in a dose dependent manner. The gene expression profiles of MNNG-HOS and 143B cells treated or not with regorafenib and analyzed by NanoString technology revealed a specific regulation of molecular pathways by regorafenib in both cell lines. The in vivo effect of regorafenib was then analyzed in immunocompetent (mouse MOS-J cells inoculated in C57Bl/6 mice) and immunodeficient (human MNNG-HOS and 143B OS cells injected in Nude mice) murine osteosarcoma models. In all the cases, a significant reduction of primary tumor growth was observed as well as a significant decrease of lung metastases compared to untreated mice. Interestingly, the cortical and trabecular bone mineral density were significantly increased in regorafenib treated mice compared to untreated groups as demonstrated by X ray microtomodensitometry in all models. Conclusions: Our results support the use of regorafenib as an alternative treatment in metastatic OS and demonstrated for the first time the its bone protective effect.
Association of immune-related adverse events and efficacy outcomes in phase II trial of consolidation nivolumab plus ipilimumab or nivolumab alone after chemoradiation in patients with unresectable stage III non–small-cell lung cancer (NSCLC).
Authors: Cynthia Wei, Sandra K. Althouse, Hirva Mamdani, Nasser H. Hanna, Greg Andrew Durm
Journal: Journal of Clinical Oncology (2023)

8565 Background: Immunotherapy has been widely incorporated into the treatment of patients with non-small-cell lung cancer. Many of these patients will experience immune-related adverse events (irAEs) that may lead to early discontinuation of therapy. Previous studies have reported that patients with Stage III and metastatic NSCLC who experienced irAEs receive fewer cycles of immunotherapy without decreased efficacy. Here we report a retrospective analysis of the association between irAEs and efficacy outcomes from the BTCRC LUN 16-081 randomized phase 2 trial of consolidation immunotherapy with nivolumab (N) plus ipilimumab (IPI) vs N alone following concurrent chemoradiotherapy in patients with unresectable Stage IIIA/IIIB NSCLC. Methods: A total of 105 eligible patients were enrolled from 9/2017 to 4/2021. Demographics, disease characteristics, and number of immunotherapy cycles received were reported in patients with and without irAEs in the two arms. Chi-square test was used for comparisons for categorical variables and Wilcoxon test for continuous variables. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). A log-rank test was used to compare groups. Results: In treatment arm A (N alone), any grade irAEs occurred in 64.8% of patients. At a follow up of 48 months, there was no significant difference in number of N cycles started (6 vs 6, p = 0.238), progression free survival (29.4 vs 31.9 mo, p = 0.897), or overall survival (NE vs. 31.9 mo, p = 0.798) in patients with and without irAEs. Patients who discontinued N because of irAEs (n = 8 or 14.8% of patients) received significantly fewer cycles of N (2 vs 6, p = &lt; .0001) and had a shorter PFS (8.2 vs. 31.9 months, p = &lt; .0001) and OS (12.3 months vs. NE, p &lt; .0001). In treatment arm B (IPI+N), any grade irAEs occurred in 84.3% of patients. At follow up of 48 months, there was no significant difference in number of IPI+N started (4 vs. 4, p = 0.260) or overall survival (NE vs. NE, p = 0.576), but there was a significantly longer PFS in those who experienced irAEs (30.9 months vs. 6.8 months, p = 0.0083). Patients who discontinued IPI+N because of irAEs (n = 18 or 35.3% of patients) received significantly fewer cycles of IPI+N (2 vs 4, p = &lt; .0001) without a significant difference in PFS (28.1 vs. 25.3 mo, p = 0.830) or OS (NE vs NE, p = 0.755). Conclusions: The occurrence of irAEs alone in both arms, regardless of number, was not associated with decreased efficacy outcomes in this exploratory analysis. However, if irAEs resulted in the discontinuation of therapy, these patients did have a shorter PFS and OS in the N alone arm. This difference was not observed in the IPI+N arm and those who experienced any irAEs in the IPI+N arm had an improved PFS.
Immuno-embolization plus PD1 antibody in metastatic uveal melanoma.
Authors: Asad Javed, Chad Davis, Mohammad Amarneh, Michele T Freesmeier, Bradley T. Loeffler, Mohammed M. Milhem
Journal: Journal of Clinical Oncology (2023)

e21592 Background: More than 90% of patients with metastatic uveal melanoma (MUM) have metastatic disease in the liver. MUM has a poor prognosis following development of liver metastasis. Control of disease progression in the liver correlates with improved survival in MUM. We present a single-institution experience of treating MUM patients with immuno-embolization (IE) of liver metastasis using GM-CSF in combination with an anti-PD1 antibody (Pembrolizumab). Methods: This retrospective study includes MUM patients who received liver-directed therapy (IE) in combination with IV Pembrolizumab at the University of Iowa. Patients selected for IE treatment had liver-predominant metastatic disease involving less than 50% of the total liver parenchyma, total bilirubin &lt; 2, serum albumin &gt; 3, and patient ECOG PS of 0-1. Alternating lobar IE was administered every 4 weeks using a combination of GM-CSF (2000 mcg) and Lipiodol. Pembrolizumab was administered IV at 200 mg every 3 weeks. Results: 11 MUM patients received a total of 58 IE treatments concurrently with IV Pembrolizumab. 4 patients achieved stable disease, and 2 patients achieved partial response as their best radiographic response during treatment. 6 patients received additional lines of therapy; of these, 4 were enrolled into clinical trials. 5 patients were alive at the time of analysis, and 2 patients were actively receiving IE plus Pembrolizumab therapy. The median overall survival (OS) from diagnosis was 25.6 months, and the median OS from the first IE treatment was 21.3 months. Complications related to IE treatments included bleeding (n = 1), severe post-procedural pain (n = 2), infection (n = 1), and anaphylactic reaction (n = 1). No unexpected immune-related side effects occurred with Pembrolizumab. Specifically, no immune-related hepatic toxicity was reported in any patient. Conclusions: Immuno-embolization of liver metastasis using GM-CSF in combination with systemic check-point inhibitor therapy is promising in the treatment of MUM patients, and had no reported immunologic hepatic toxicity in a single-institution patient cohort. The treatment combination is currently being evaluated in a prospective clinical trial (NCT03472586).
Preliminary survival outcomes and toxicities in patients with retroperitoneal sarcoma treated with radiotherapy.
Authors: Hao-shen Cheng, Yi-Chun Liu
Journal: Journal of Clinical Oncology (2023)

e23524 Background: To investigate the survival outcomes, the treatment toxicities, and the recurrence pattern of nineteen patients with retroperitoneal sarcoma treated with radiotherapy. Methods: The inclusion criteria for this retrospective study were previously untreated retroperitoneal sarcoma who had received radiotherapy. From March 2016 to June 2022, the chart records and images of 22 eligible patients were reviewed. There were ten males and twelve females, and their ages ranged from 34 to 80 years old (median 55). Sixteen patients (72.7%) had a liposarcoma, four patients (18.3%) had a leiomyosarcoma, one patient (4.5%) had a spindle cell sarcoma, and one patient (4.5%) had a malignant peripheral nerve sheath tumor with heterologous rhabdomyosarcomatous and liposarcomatous differentiation. At diagnosis, four patients (18.1%) had a stage I-II disease, eighteen patients (77.4%) had a stage III disease, and only one patient (4.5%) had a stage IV disease. Twenty one patients (95.5%) received operation, and nineteen of them had a positive or close ( &lt; 1mm) surgical margin. Nineteen patients (86.4%) received adjuvant radiotherapy (median dose 5400cGy, ranging 5000 to 6300cGy), one patient (5.3%) received neoadjuvant radiotherapy (5000cGy), one patient received definitive chemoradiotherapy (7000cGy), and one patient received palliative radiotherapy (3000cGy) to bone metastasis. Results: The medial follow-up was 32 months, and the two-year overall survival rate was 79.8%. Acute toxicities of radiotherapy included gastrointestinal toxicities (grade 1-2: 9 patients), nausea (grade 1-2: 7 patients, grade 3-4: 3 patients), vomiting (grade 1-2: 3 patients, grade 3-4: 2 patients), neutropenia (grade 1-2: 2 patients, grade 3-4: 1 patients), and fatigue (grade 1-2: 5 patients). In patients without metastatic disease at diagnosis, two-year overall survival rate was 84.0%, and two-year disease-free survival rate was 62.9%. There were 8 recurrences (1 local alone, 2 distant metastasis alone, 1 local plus regional, 3 local plus distant metastasis, and 1 local plus regional plus distant metastasis), and 5 deaths. Recurrent metastatic locations included lung (n = 1), liver (n = 1), bone (n = 2), peritoneum (n = 1), distant lymph nodes (n = 1), and soft tissue of thigh (n = 1). One patient with metastatic disease at diagnosis expired due to disease progression with 8 months survival. Conclusions: Radiotherapy in retroperitoneal sarcoma provided an acceptable two-year survival rate with tolerable toxicities, but recurrence rate was still high. About 75.0% of recurrent events consisted of local recurrence, so close follow up of primary tumor area is necessary.
Biologic profile to predict overall survival in non-metastatic breast cancer: A latent class analysis on aging biomarkers.
Authors: Claire Falandry, Barbara Anna Henk Brouwers, Cindy Kenis, Ann Smeets, Patrick Neven, Charlotte Cuerq, Karim Chikh, Sigrid Hatse, Hans Wildiers
Journal: Journal of Clinical Oncology (2023)

12037 Background: The aging process is heterogeneous and the result of different biological mechanisms. Blood biomarkers involved in the aging process, aside from comprehensive geriatric assessment, may help clinicians when facing equivocal therapeutic decisions, for example adjuvant treatment at high risk of toxicities. Methods: This study was conducted on a previously published cohort (PMID 25989735) including 162 patients aged ≥70 years (“Old”) and 82 patients aged ≤60 years (“Young”) with newly diagnosed non-metastatic breast cancer. Serum samples collected from all patients at breast cancer diagnosis, before any treatment were available from the extensive Leuven blood biobank. Overall survival was evaluated with October 7, 2022 as data cutoff. A panel of blood aging biomarkers attributed to inflammation: IL6, MCP1, RANTES, telomere shortening: telomeric DNA ratio T/S, telomeric dysfunction: CRAMP, chitinase activity, and anabolism : IGF1. Considering a high risk of collinearity, we performed a latent class analysis (LCA) on the whole cohort, to delineate the respective roles of inflammaging, replicative senescence and sarcopenia on patient clusters. Results: In univariate analysis were significantly associated with a poorer survival: high MCP1, hazard ratio (HR) = 1.57 (95%CI 1.32-1.87), high chitinase activity, HR = 1.33 (95%CI 1.12-1.57), and low IGF1, HR = 1.76 (95%CI 1.47-2.11). The biomarkers correlation matrix identified a significant correlation of Chitinase activity with MCP1, IGF1, CRAMP; of CRAMP with IL6; and IGF1 with T/S ratio. LCA identified 2 biologic profiles within the population, representing 137 (56.1%, class 1) and 107 (43,9%, class 2) patients. Class 1 was associated with a significantly poorer overall survival: HR = 3.52 (95%CI 2.28-5.45), and age-adjusted HR = 1.77 (95%CI 1.12-2.80). The best predictors for class 1 membership were low IGF1 (89%), high MCP1 (82%), high chitinase activity (79%), high IL6 (69%). Class 1 represented 77% of the “Old” and 15% of the “Young” populations. Conclusions: Our results delineate an unfavorable biologic profile that transcends chronological age and significantly predicts a poorer overall survival, underpinned by markers of both inflammaging, telomeric dysfunction and sarcopenia. The strong correlation between markers argues for a unique underlying biological pathway. Noteworthy, high IGF1, usually considered as a risk factor for breast cancer progression, was associated with a better prognosis. Low IGF1, high chitinase activity and high MCP1 appear as promising predictive biomarkers.
The impact of 4R oncology model on patient self management and satisfaction in lung versus breast cancer.
Authors: Julia R. Trosman, Christine B. Weldon, Elizabeth Shurell Linehan, Nancy P. Gordon, Marti Hennings, Thea Abbe, Henie James, Jed Abraham Katzel, Chun Fai Ng, Megumi Tomita, Jeffrey B. Velotta, Lori C. Sakoda, Kimberly Beringer, Arliene Ravelo, Zheng Zhu, Bruce Rapkin, Raymond Liu
Journal: Journal of Clinical Oncology (2023)

e18703 Background: Proposed under NCI ASCO Teams project, the 4R Oncology model (Right Info/Care/Patient/Time) facilitates patient self management (PSM) and team based care delivery with a novel 4R Care Sequence plan (JOP 2016). 4R has been shown to improve PSM in breast cancer (JCOOP 2021), but its impact in other cancers is unknown. Also, the 4R effect on patient satisfaction – a care quality aspect important at patient and institutional levels - has not been evaluated. We examined and compared 4R impact on PSM and patient satisfaction in lung (LC) and breast (BC) cancers at 3 centers of a large health system Oct 2020 - Dec 2021. Methods: Surveys of patient cohorts: 4R cohort who received 4R plans and historical control who received care pre-4R. Cohorts included BC stages 0-3 and all LC stages. See Table for metrics. Results: Survey response rates: 53% (control), 42% (4R). All PSM and satisfaction metrics significantly improved in 4R vs. control groups for the combined cohort of both cancers (Table). LC and BC patients significantly benefited from 4R vs control in 2 PSM metrics (b, c). LC patients benefited more than BC patients in 1 PSM and 3 satisfaction metrics (a, g, i, j). For other metrics (d, e, f, h) benefits in LC occurred in the same direction and same magnitude as in BC, but were not significant, likely due to smaller group size. Among 4R patients, similar ratios of LC and BC patients deemed 4R useful (76%, 78%, p = .7) (data not shown). Conclusions: 4R improved self management and satisfaction among patients with lung or breast cancer. Notably, it helped lung cancer patients who are typically older and sicker than breast cancer patients to better understand their cancer and manage their care. It also helped lung cancer patients feel more respected and taken seriously, suggesting that 4R countered the stigma and guilt often experienced by these patients. Variable impact in some metrics between lung and breast cancers suggest different self management needs relevant to these metrics. Further model refinement should address these differences. [Table: see text]